Recently, much research has been done on implantable or injectable drug delivery systems comprising biodegradable polymers and a pharmaceutically active agent. Ideally these systems provide for the controlled release of the active agent while the polymer carrier degrades to non-toxic, soluble monomers, thereby obviating the need for surgical removal of the device. Of these biodegradable polymers, polyanhydrides are particularly attractive because they demonstrate a near zero-order drug release and degrade relatively rapidly in vivo to highly biocompatible monomeric diacids. High molecular weight polyanhydrides are especially useful for biomedical applications because of their superior physicochemical and mechanical properties including film forming properties and relatively high tensile strength.
High molecular weight polyanhydrides are typically prepared by melt polycondensation in which a mixture of the individually prepared prepolymers are heated at a temperature of about 150-220.degree. C. under a vacuum of about 10.sup.-4 to 1 mm Hg until a polymer having the desired properties is obtained (see U.S. Pat. No. 4,789,724; and Domb, A. J. and Maniar, M. J. Poly. Sci: Part A, 1993, 31, 1975). However, the extension of the melt polycondensation method to the pilot plant or commercial production presents a number of problems. The reaction time and temperature necessary for the reaction appear to be dependent on the scale of the reaction, thereby making it difficult to predict reaction conditions. Deviations from the reported reaction conditions may result in polymers having undesirable properties. In addition, the high temperature of the reaction, mixing of the thick molten mass during melt polycondensation, and high vacuum requirement are undesirable. Isolation of the product produced by melt polymerization may be difficult and unsafe.
Moreover, polyanhydrides produced by melt poycondensation techniques which are to be used in implant devices may have higher than desired levels of carboxylic acid anhydride.
It would be beneficial if an alternative to melt polycondensation eliminated problems associated with the use of polyanhydrides made by melt polycondensafion.